ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina—Summary Article : A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina)

Both lipid-modifying therapy and antioxidant vitamins are thought to have benefit in patients with coronary disease. We studied simvastatin-niacin and antioxidant-vitamin therapy, alone and together, for cardiovascular protection in patients with coronary disease and low plasma levels of HDL. In a three-year, double-blind trial, 160 patients with coronary disease, low HDL cholesterol levels and normal LDL cholesterol levels were randomly assigned to receive one of four regimens: simvastatin plus niacin, vitamins, simvastatin-niacin plus antioxidants; or placebos. The end points were arteriographic evidence of a change in coronary stenosis and the occurrence of a first cardiovascular event (death, myocardial infarction, stroke, or revascularization). The mean levels of LDL and HDL cholesterol were unaltered in the antioxidant group and the placebo group; these levels changed substantially (by -42 percent and +26 percent, respectively) in the simvastatin-niacin group. The protective increase in HDL2 with simvastatin plus niacin was attenuated by concurrent therapy with antioxidants. The average stenosis progressed by 3.9 percent with placebos, 1.8 percent with antioxidants (P=0.16 for the comparison with the placebo group), and 0.7 percent with simvastatin-niacin plus antioxidants (P=0.004) and regressed by 0.4 percent with simvastatin-niacin alone (P<0.001). The frequency of the clinical end point was 24 percent with placebos; 3 percent with simvastatin-niacin alone; 21 percent in the antioxidant-therapy group; and 14 percent in the simvastatin-niacin-plus-antioxidants group. Simvastatin plus niacin provides marked clinical and angiographically measurable benefits in patients with coronary disease and low HDL levels. The use of antioxidant vitamins in this setting must be questioned.

Both attenuated heart rate recovery following exercise and the Duke treadmill exercise score have been demonstrated to be independent predictors of mortality, but their prognostic value relative to each other has not been studied. To assess the associations among abnormal heart rate recovery, treadmill exercise score, and death in patients referred specifically for exercise electrocardiography. Prospective cohort study conducted in an academic medical center between September 1990 and December 1997, with a median follow-up of 5.2 years. A total of 9454 consecutive patients (mean [SD] age, 53 [11] years; 78% male) who underwent symptom-limited exercise electrocardiographic testing. Exclusion criteria included age younger than 30 years, history of heart failure or valvular disease, pacemaker implantation, and uninterpretable electrocardiograms. All-cause mortality, as predicted by abnormal heart rate recovery, defined as failure of heart rate to decrease by more than 12/min during the first minute after peak exercise, and by treadmill exercise score, defined as (exercise time) - (5 x maximum ST-segment deviation) - (4 x treadmill angina index). Three hundred twelve deaths occurred in the cohort. Abnormal heart rate recovery and intermediate- or high-risk treadmill exercise score were present in 20% (n = 1852) and 21% (n = 1996) of patients, respectively. In univariate analyses, death was predicted by both abnormal heart rate recovery (8% vs 2% in patients with normal heart rate recovery; hazard ratio [HR], 4.16; 95% confidence interval [CI], 3.33-5.19; chi(2) = 158; P<.001) and intermediate- or high-risk treadmill exercise score (8% vs 2% in patients with low-risk scores; HR, 4.28; 95% CI, 3.43-5.35; chi(2) = 164; P<.001). After adjusting for age, sex, standard cardiovascular risk factors, medication use, and other potential confounders, abnormal heart rate recovery remained predictive of death (among the 8549 patients not taking beta-blockers, adjusted HR, 2.13; 95% CI, 1.63-2.78; P<.001), as did intermediate- or high-risk treadmill exercise score (adjusted HR, 1. 49; 95% CI, 1.15-1.92; P =.002). There was no interaction between these 2 predictors. In this cohort of patients referred specifically for exercise electrocardiography, both abnormal heart rate recovery and treadmill exercise score were independent predictors of mortality. Heart rate recovery appears to provide additional prognostic information to the established treadmill exercise score and should be considered for routine incorporation into exercise test interpretation. JAMA. 2000;284:1392-1398.

Heart disease is a major cause of illness and death in women. To understand better the role of estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects. We randomly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of conjugated estrogen per day, 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (+/-SD) of 3.2+/-0.6 years. Base-line and follow-up coronary angiograms were analyzed by quantitative coronary angiography. Estrogen and estrogen plus medroxyprogesterone acetate produced significant reductions in low-density lipoprotein cholesterol levels (9.4 percent and 16.5 percent, respectively) and significant increases in high-density lipoprotein cholesterol levels (18.8 percent and 14.2 percent, respectively); however, neither treatment altered the progression of coronary atherosclerosis. After adjustment for measurements at base line, the mean (+/-SE) minimal coronary-artery diameters at follow-up were 1.87+/-0.02 mm, 1.84+/-0.02 mm, and 1.87+/-0.02 mm in women assigned to estrogen, estrogen plus medroxyprogesterone acetate, and placebo, respectively. The differences between the values for the two active-treatment groups and the value for the placebo group were not significant. Analyses of several secondary angiographic outcomes and subgroups of women produced similar results. The rates of clinical cardiovascular events were also similar among the treatment groups. Neither estrogen alone nor estrogen plus medroxyprogesterone acetate affected the progression of coronary atherosclerosis in women with established disease. These results suggest that such women should not use estrogen replacement with an expectation of cardiovascular benefit.